Publications by authors named "William H J Norton"
Article Synopsis
- Environmental factors, particularly environmental enrichment (EE), influence the development and severity of neuropsychiatric disorders, especially externalizing disorders that involve impulsive and aggressive behaviors.
- The study focused on zebrafish with a gene linked to impulsivity and attention deficits (adgrl3.1), showing that those raised in enriched environments exhibited reduced anxiety and improved attention but continued to display impulsive behaviors.
- These results indicate that while EE can help alleviate some symptoms associated with externalizing and internalizing disorders, impulsivity is more resistant to environmental modifications.
Social isolation intensifies adgrl3.1-related externalizing and internalizing behaviors in zebrafish.
Prog Neuropsychopharmacol Biol Psychiatry
November 2024
Article Synopsis
- Externalizing disorders (EDs), marked by behaviors like aggression and hyperactivity, arise from complex gene-environment interactions, but the specifics are not fully understood.
- Research using adgrl3.1 knockout zebrafish showed that social isolation worsens anxiety, abnormal behaviors, and memory issues, particularly in genetically predisposed individuals.
- The study highlights the importance of considering both genetic and environmental factors in diagnosing and treating EDs, emphasizing the need for more integrated approaches.
Article Synopsis
- X-linked intellectual disability (XLID) is a genetic condition affecting primarily males, leading to cognitive and physical impairments and associated with genetic defects on the X chromosome.
- Researchers identified specific genetic variants in the SRPK3 gene linked to XLID in nine patients and developed a zebrafish model to study SRPK3's function.
- The study found that mutations in SRPK3 are tied to common symptoms seen in XLID, including intellectual disability and abnormal eye movement, emphasizing its critical role in neurodevelopmental disorders.
Article Synopsis
- - Antidepressants, particularly the tricyclic drug amitriptyline (AMI), are widely prescribed, raising concerns about their effects on non-target aquatic organisms like fish due to potential environmental exposure.
- - A study using zebrafish revealed that AMI accumulates in their bodies, converts to an active metabolite, and impacts gene expression related to serotonin transport even at low, environmentally relevant concentrations.
- - While higher concentrations of AMI affected fish behavior (like increased hatch rates and decreased movement), the overall low risk to fish populations may be underestimated due to factors like the ongoing increase in prescription rates and the presence of other drugs acting similarly.
RBFOX1 is a highly pleiotropic gene that contributes to several psychiatric and neurodevelopmental disorders. Both rare and common variants in RBFOX1 have been associated with several psychiatric conditions, but the mechanisms underlying the pleiotropic effects of RBFOX1 are not yet understood. Here we found that, in zebrafish, rbfox1 is expressed in spinal cord, mid- and hindbrain during developmental stages.
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- The optokinetic reflex (OKR) assays in zebrafish are useful for studying various eye and brain disorders, but there's a lack of standard reporting guidelines for these assays.
- A systematic literature review of 109 research papers identified key factors like larval characteristics and stimulus parameters that should be included in future studies.
- To improve research transparency and reliability, the authors developed the zebrafish optokinetic (ZOK) reflex minimal reporting guideline based on their findings.
Article Synopsis
- The optokinetic reflex (OKR) is crucial for assessing visual system development in infants and can be effectively studied using zebrafish larvae due to their rapid growth and suitability as a model organism.
- This research introduces a new, portable OKR assay that utilizes the Samsung Galaxy Z Flip, contrasting it with a traditional LCD setup for zebrafish testing.
- The study found that both assays successfully measured eye movements with similar accuracy and no significant differences in results, highlighting the advantages of the new approach in terms of convenience and cost-effectiveness.
adgrl3.1-deficient zebrafish show noradrenaline-mediated externalizing behaviors, and altered expression of externalizing disorder-candidate genes, suggesting functional targets for treatment.
Barbara D Fontana Florian Reichmann Ceinwen A Tilley Perrine Lavlou Alena Shkumatava William H J Norton
Transl Psychiatry
October 2023
Article Synopsis
- Externalizing disorders (ED) are a significant public health issue with strong genetic links, making genes like ADGRL3 important for study.
- Research using adgrl3.1 zebrafish highlighted behavioral traits such as high impulsivity, risk-taking, and hyperactivity, which are typical of ED.
- Atomoxetine can alleviate these behaviors, indicating a role of noradrenergic systems, while brain studies reveal new genetic pathways that may contribute to understanding and treating ED.
Article Synopsis
- - Social isolation negatively impacts health, leading to increased anxiety and changes in gene expression in zebrafish at different life stages after just 2 weeks of isolation.
- - Upon reintroduction to social environments, most gene expression levels returned to normal within 24 hours, except for angptl4, which remained elevated, indicating a possible adaptive response.
- - The study suggests that angptl4 plays a crucial role in how organisms respond to social isolation, with notable differences between young and aging zebrafish, emphasizing the significance of social interactions for mental health.
Article Synopsis
- Intellectual disability (ID) is a common disorder that affects cognitive and adaptive functioning, with X-linked intellectual disability (XLID) impacting 1.7 out of 1,000 males due to mutations on the X chromosome.
- Researchers identified three specific mutations in a gene related to XLID in seven patients from different families, all of whom exhibited common symptoms such as intellectual disability and abnormal eye movements.
- A zebrafish model was created to study the gene's function, revealing that knockout (KO) zebrafish had significant developmental issues, supporting the gene's role in learning and psychiatric disorders.
Article Synopsis
- * Using a genetic model of zebrafish, researchers found that certain non-stimulant drugs could reduce hyperactivity but often interfered with sleep patterns; this includes testing a library of compounds to identify effective alternatives.
- * They discovered five potential new therapeutics, including moxonidine, which shows promise not only in reducing hyperactivity but also in cognitive effects, hinting at new mechanisms underlying ADHD therapy through imidazoline receptors.
Article Synopsis
- Using different species to study complex human psychiatric conditions like ADHD can reveal important evolutionary patterns in behaviors such as movement, attention, and impulsivity.
- This text focuses on the use of zebrafish as a model organism for studying ADHD-like behaviors and discusses the benefits and difficulties associated with this approach.
- It provides a review of current research on ADHD in zebrafish and explores how this research could help speed up the discovery of new treatments for ADHD.
Article Synopsis
- - The study investigates mirror aggression in zebrafish, a behavior where they respond aggressively to their own reflection, revealing variations in aggression levels among individuals.
- - Using selective breeding, researchers categorized zebrafish into high-aggression (HAZ) and low-aggression (LAZ) groups and found that HAZ showed more aggression and less anxiety than LAZ after generations of breeding.
- - Genetic analysis revealed hundreds of differentially expressed genes linked to various biological functions and identified multiple pathways associated with aggression, highlighting a strong genetic influence on aggressive behavior in zebrafish.
Article Synopsis
- Genetic variants in YWHAZ are linked to psychiatric disorders like autism and schizophrenia, impacting neurodevelopment in both humans and mice.
- In zebrafish, ywhaz is found to be crucial for neuronal development, with its expression changing from widespread in early stages to specific in adult Purkinje cells, which are often impaired in autistic individuals.
- Research showed that knocking out ywhaz leads to altered brain activity, decreased monoamines, and behavior changes in adult fish, indicating its role in neuronal connectivity and neurotransmission regulation.
Article Synopsis
- * Most studies indicate that the levels of antidepressants found in nature do not significantly impact fish based on standard risk assessment measures, although some behavioral changes have been observed.
- * There is a need for more research to fill gaps in current data, particularly focusing on long-term effects, behavioral impacts on fish, and exposure to multiple substances, to better understand the risks associated with antidepressants in aquatic ecosystems.
Article Synopsis
- The study investigates the role of the ubiquitin ligase CHIP in zebrafish and its implications for diseases linked to CHIP deficiency, particularly spinocerebellar ataxias (SCAR16/SCA48).
- Researchers created a zebrafish mutant with a truncated CHIP protein, observing that this mutation led to reduced activity in tagging misfolded proteins for degradation.
- Although the mutant zebrafish did not show severe brain atrophy, they exhibited anatomical changes in Purkinje cells and altered behaviors, highlighting zebrafish as a valuable model for studying the consequences of impaired ubiquitin ligase activity.
Article Synopsis
- Early-life stress (ELS) can lead to various long-term effects, such as heightened disease vulnerability or increased resilience in adulthood.
- This study used zebrafish larvae exposed to chronic unpredictable early-life stress (CUELS) for 7 or 14 days to examine changes in boldness and stress reactions in a novel environment.
- Results showed that 7 days of CUELS increased boldness but decreased anxiety-like responses without altering cortisol levels, highlighting zebrafish as a useful model for understanding ELS impacts on behavior.
Article Synopsis
- * A study identified ebselen, a small molecule, that binds covalently to 14-3-3 proteins, decreasing their stability and disrupting their interaction with partner proteins like Ser19-phosphorylated tyrosine hydroxylase.
- * Ebselen showed promise in lowering 14-3-3 protein levels in cells and zebrafish models, leading to effects similar to lithium, suggesting its potential as a safer alternative for treating conditions related to these proteins.
Article Synopsis
- * Zebrafish are a promising model organism for investigating the mechanics of social interactions due to their genetic similarities to humans and ease of experimental use.
- * Studying zebrafish can provide insights into how social interactions affect health, potentially revealing important molecular and physiological changes linked to isolation and social behavior.
Article Synopsis
- - Model fish species like sticklebacks and zebrafish are used for DNA sampling, typically through fin clipping, which can harm the fish.
- - An alternative method, skin swabbing, is less invasive than fin clipping and shows reduced cortisol levels and behavioral changes immediately after the procedure.
- - While swabbing leads to less immediate stress and variability in results, it may cause delayed behavioral changes, making it a more refined option to enhance fish health and welfare during DNA collection.
Chronic unpredictable early-life stress (CUELS) protocol: Early-life stress changes anxiety levels of adult zebrafish.
Prog Neuropsychopharmacol Biol Psychiatry
June 2021
Article Synopsis
- Early-life stress in zebrafish can lead to different outcomes, such as increased risk of psychiatric disorders or resilience, depending on the duration of stress exposure.
- A chronic unpredictable early-life stress (CUELS) protocol was applied to assess the effects of various mild stressors on zebrafish over different time periods (0, 1, 3, 7, and 14 days).
- Zebrafish exposed to 7 days of CUELS exhibited reduced anxiety-like behavior, while those exposed to 14 days developed increased anxiety, suggesting a potential link between early stress duration and anxiety levels.
Article Synopsis
- - The study investigates the role of the histamine H3 receptor (Hrh3) in aggression behavior using a zebrafish model, revealing its significant impact on aggression and anxiety levels.
- - Researchers created a Hrh3 null mutant line using CRISPR and analyzed changes in behavior and neural activity through imaging techniques, finding that inactivation of Hrh3 leads to reduced aggression and increased anxiety.
- - The findings suggest that Hrh3 signaling is crucial for aggression and anxiety regulation, indicating potential therapeutic targets for addressing similar human conditions characterized by heightened aggression.
Article Synopsis
- Genome-wide screenings have linked the cell adhesion molecule Cadherin-13 (CDH13) to neurodevelopmental disorders, but its exact role in these conditions is still not well understood.
- CDH13 is crucial for proper brain development, influencing aspects like neurite outgrowth and the serotonin (5-HT) system, particularly through interactions between neurons and radial glia.
- Using a specialized mouse model that lacks CDH13 specifically in 5-HT neurons, researchers found increased 5-HT neuron density and abnormal behavior patterns in adulthood, highlighting the importance of CDH13 in the development of 5-HT pathways related to neurodevelopmental disorders.
Article Synopsis
- Aggression is a symptom of psychiatric disorders, but current treatment drugs are non-specific and may cause side effects.
- Researchers tested 94 drugs and found that caffeine and sildenafil specifically reduce aggression in zebrafish, with distinct effects on attention and impulsivity.
- The study indicates that juvenile zebrafish can be a useful model for screening drugs that target aggression and offers insights into the neural mechanisms involved.
Reelin Signaling Controls the Preference for Social Novelty in Zebrafish.
Front Behav Neurosci
September 2019
Article Synopsis
- - Reelin (Reln) is a critical extracellular glycoprotein involved in brain development and function, particularly in neuron migration and synaptic processes.
- - Research indicates that mutations in the RELN gene are linked to human disorders like autism, schizophrenia, and Alzheimer's disease.
- - This study observes that mutant zebrafish with altered Reln signaling show reduced social interaction preferences and increased serotonin signaling, suggesting they can serve as a model for studying related human diseases.